Blocking a small but powerful piece of genetic material appears to prevent a major form of diabetes-related kidney disease, according to a study led by researchers in City of Hope’s Division of Molecular Diabetes Research.
The findings, published online Jan. 5 in the Journal of the American Society of Nephrology, point to a potential new drug target for treating diabetic nephropathy, the leading cause of kidney failure in the U.S.
Mitsuo Kato, left, and Sumanth Putta (Photo by Darrin S. Joy)
Scientists have been delving into the world of microRNAs, or miRNAs, for more than a decade. These short pieces of genetic material have been shown to have a huge impact on controlling key cellular functions.
One miRNA, called miR-192, controls production of collagen, a fibrous substance that helps make up tissues such as tendons and ligaments.
In some people with diabetes, kidney cells overproduce collagen. The resulting life-threatening condition, called renal fibrosis, can clog the kidneys and eventually shut them down.
The researchers, led by postdoctoral fellow Sumanth Putta, Ph.D., research assistant professor Mitsuo Kato, PhD, and division director Rama Natarajan, Ph.D., National Office Products Industry Professor in Diabetes Research, developed a molecule that inhibits miR-192, preventing it from boosting collagen production. Their first tests of the drug proved promising.
When the researchers tried the inhibitor in a laboratory mouse model that mimics diabetes, they saw that it reduced collagen gene expression in the kidney as well as expression of two other genes that boost renal fibrosis: transforming growth factor-beta and fibronectin.
“We also saw a reduction in proteinuria in the treated mice,” Putta said. Proteinuria is an abnormal build-up of protein in urine and a key indicator of kidney disease.
The researchers cite the study as strong evidence that an anti-miRNA-based therapy could be developed to help treat diabetic nephropathy.
Their continuing studies aim to eventually advance the approach to clinical trials.
Additional authors on the study include Linda Lanting of City of Hope, Guangdong Sun, Ph.D., of Second Hospital of Jilin University in Changchun, Jilin, China, and Gregory Lawson, Ph.D., of the University of California, Los Angeles.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases.